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Roland Schuele - "Research cannot be predicted"

Professor Roland Schuele from the University Women’s Hospital in Freiburg originally studied biochemistry. Nowadays, Schuele is researching the development of prostate cancer. During his scientific career, he has learnt that research cannot be steered in a particular direction. “It develops and we follow it,” said Schuele who has been able to gain astonishing insights into the molecular processes in tumour cells.

Prof. Roland Schuele (Photo: Prof. Dr. Roland Schuele)
Schuele began his scientific studies in Kiel in 1977, where he started with marine chemistry. “Back then, Kiel in the very north of Germany was as far as I could get away from Neuenstadt, a small city close to Heilbronn in the south of Germany,” said Schuele, who soon found chemistry too boring. He developed an interest in living organisms and wanted to understand how cells functioned. And he was lucky: After his pre-diploma he applied to Tübingen University and was accepted as a biochemistry student.

Schuele soon developed an interest in hormones. He was fascinated by the fact that these small molecules controlled such a vast range of human behaviour. “Sexual behaviour, eating, growth: they regulate almost everything,” said Schuele. In his degree thesis, Schuele therefore focused on the molecular biology of hormones where he had his first contacts with genetics. “Back then, genetic engineering was a fledgling area,” recalls Schuele who did his doctorate (completed in 1988) at one of the major centres of genetics, the Max Planck Institute of Biochemistry in Martinsried. His studies were an extremely successful and exciting time, during which he examined the basic mechanisms of hormone regulation.

From hormones to cancer

The molecular biology of hormones eventually took him to the Salk Institute in California, where he spent three years as a post-doc in the department of Ronald Evans, one of the leading scientists in the field. “It was a fantastic laboratory with fantastic scientists,” said Schuele recalling what he refers to as some of the best years in his career. He returned to Europe in 1991 and spent two years as the head of a research group at Sandoz in Basel, Switzerland. In 1993, he accepted a post at the Tumour Biology Centre at the University of Freiburg and finally came into contact with the area of cancer research, in which he investigated the molecular basis of prostate cancer, which has an annual incidence of approximately 500,000 cases in Europe and the USA. “This field had a lot to offer because not much had been known about this type of cancer,” said Schuele, adding that “we could head off in completely new directions, anything was possible.”

He habilitated in 1999 and accepted a post as the head of the Department of Molecular Gynaecology at the University Women’s Clinic because the Tumour Biology Centre decided to abandon basic prostate research for financial reasons. The Women’s Hospital was about to set up an endocrinological department and Schuele seemed to be the sought-after specialist since prostate cancer had something to do with hormones, male sex hormones (androgens, of which testosterone is one example) to be more precise.

For many patients a disease with no hope

A normal prostate (arrow points towards a cell in which the enzyme LSD1, which was discovered by Prof. Schuele, is found. (Photo: Prof. Roland Schuele)

Androgens affect the gene activity in the prostate tumour cells and this causes the tumour to grow uncontrollably. For this reason, doctors often use androgen antagonists to treat prostate cancer. These are substances that inhibit the effect of androgens. However, this only works in about two thirds of patients; in one third of patients the tumour continues to grow for still unknown reasons and does so completely independently from the hormones. It even grows if it has no contact with the hormones. “In such cases, androgen antagonists do not help. And for these patients, there is no remedy available.”

Schuele’s research developed more quickly than expected; and it also went in a completely different direction than expected. And this research even seemed to offer a potential starting point for cancer therapy. Schuele found the enzyme LSD1 (lysine-specific demethylase 1) in the nuclei of prostate tumour cells, which affects the transcription of some genes. These genes are the same genes as those that are switched on by male sex hormones and whose uncontrollable activity drives the growth of the tumour.

If this enzyme is blocked with a chemical inhibitor, then the tumour stops growing. At least, this is the result of initial experiments carried out with isolated tumour cells. And the principle functions independently of the presence of androgens. “This raises hopes that there exists a potential to use such inhibitors to treat cancer patients who have ceased to respond to androgen antagonists,” said Schuele.

Against the central dogma

His insights were also groundbreaking in a more theoretical respect. The enzyme LSD1 is what is referred to as an epigenetic factor. Such factors can activate or silence DNA stretches by attaching or removing small molecules. This leaves a signature for transcription enzymes, which determines which proteins the cell finally produces. Initially, it was assumed that the signature was rigid and remained the same until the death of the cell. “This was for a long time the central dogma of epigenetics,” said Schuele whose results however show that the contrary is the case; that this signature is very dynamic and changes repeatedly.

In the meantime, approximately 30 epigenetic factors have been found that are similar to the enzyme discovered by Schuele. The new research area has developed rapidly and a completely new field has opened up for the pharmaceutical industry. In 2004 within a few months, Schuele received three offers from other universities to head up their institutes. But the Freiburg Women’s Hospital did not want to let him go and offered him something even better. Schuele accepted and is curious to find out what kind of discoveries he will make in the future. It is impossible to predict in research. Research develops gradually and scientists follow the discoveries. And this is something that never ceases to fascinate him.

Further information:
Prof. Dr. rer. nat. Roland Schuele
University Women's Hospital and Centre for Clinical Research
University of Freiburg
Breisacherstrasse 66
79106 Freiburg
Tel.: +49 (0)761/270-6310
Fax: +49 (0)761/270-6311
E-mail: roland.schuele(at)uniklinik-freiburg.de

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/roland-schuele-research-cannot-be-predicted